Armodafinil
The longer-acting R-enantiomer of modafinil, approved for the same wakefulness indications. It produces comparable clinical benefits with a slightly more sustained plasma profile, and shares modafinil's relatively favourable tolerability.
01 Overview
Armodafinil is the purified R-(-)-enantiomer of the racemic drug modafinil, approved by the FDA in 2007. Because the R-enantiomer is eliminated more slowly, once-daily dosing can maintain higher afternoon plasma concentrations than an equivalent dose of racemic modafinil.
Registrational trials in narcolepsy, obstructive sleep apnoea and shift-work sleep disorder demonstrated reduced sleepiness and improved wakefulness. Its side-effect profile mirrors modafinil, including headache, nausea and insomnia, with the same rare risk of serious hypersensitivity reactions.
02 Mechanism
Same as modafinil: dopamine transporter inhibition raising extracellular dopamine, with downstream effects on orexin, histamine and noradrenaline promoting wakefulness.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Standard therapeutic | 150–250 mg/day | Oral | 150 mg or 250 mg once in the morning depending on indication. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced sleepiness / increased wakefulnessImproves objective and subjective wakefulness in narcolepsy, OSA and shift-work disorder. | Large in sleep disorders | Clinical | |
| Improved sustained attentionEnhances vigilance, particularly under fatigue. | Small-to-moderate | Clinical | |
| Sustained afternoon alertnessLonger plasma exposure can maintain late-day wakefulness better than racemic dosing. | Modest | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| HeadacheDose-related headache is the most frequently reported adverse effect. | Mild | Most common | Clinical | |
| InsomniaSleep-onset difficulty, accentuated by the long half-life. | Moderate | Common | Clinical | |
| Serious hypersensitivity / skin reactionsRare reports of severe rash and multi-organ hypersensitivity, as with modafinil. | Life-threatening | Rare but serious | Clinical |